Central nervous system injury and disease (e.g. stroke, spinal cord injury, Parkinson's disease) affects millions of people world-wide, leaving the afflicted with significantly compromised function. For example, spinal cord injury leads to an interruption in the neural signals between the brain and the intact motor neurons below the injury site, and often causes the loss of function in organs and body parts below the level of the injury (e.g. the loss of standing, walking and sensation in the lower extremities, loss of bladder control, etc.).
Numerous strategies to restore lost neural signalling exist such as, for example, the development of implanted neuroprosthetic devices that are capable of interfacing and integrating with the nervous system to stimulate and/or record tissue activity. Intraspinal microstimulation (ISMS) is one such neuroprosthetic technique that involves the implantation of micro-sized-electrodes within the spinal cord above or below the site of injury. Electrical stimulation of the microelectrodes can overpass the interrupted neural signal and restore activation to the remaining motoneuronal pools and elements of the neural networks involved in walking, reaching, etc.
Some neuroprosthetic implants for restoring neural signalling comprise 8-12 microelectrodes individually implanted into each side of the spinal cord. The electrodes are manually positioned, allowing for flexibility of placement within the cord. However, the electrodes themselves are very fine and difficult to handle, and the process is susceptible to placement errors which can reduce the overall accuracy and efficiency of the implant.
Other neuroprosthetic implants comprise the use of arrays of electrodes that are held together by a base. The use of an array of electrodes improves the accuracy of electrode placement, but the mechanical and electrical stability of such remains unknown.
For instance, rigid, glassy polymer, ceramic or silicon base arrays such as, for example, the Utah, Mich. and Huntington Medical Research Institute (HMRI) arrays are capable of recording from or stimulating various brain regions. Such rigid arrays, however, are known to cause adverse inflammatory responses in the neural tissue with which they interface, when they are used with tissue that deforms during daily motion (e.g. elongation, bending or rotation), such as the spine. It is desirable to develop a microelectrode array capable of mechanical harmony with neural tissue, without impeding the natural deformation of the tissue during movement.
Flexible-base electrode arrays are also known such as, for example, flexible-based intracortical arrays consisting of a polyimide base. However, a polyimide base, having a modulus of elasticity of 2.97 GPa may not provide accurate mechanical and geometrical interfacing with sensitive tissues such as neural cells, the brain, and the spinal cord, which have been estimated to have an elastic modulus of between approximately 0.1 kPa to 150 MPa, depending upon the presence of absence of pia and dura mater.
One approach to improving the mechanical properties of microelectrode arrays in vivo has been to engineer devices out of biodegradable materials (e.g. polyethylene glycol) that will gradually erode upon implantation, leaving only the electrodes in place. Alternatively, bases having a bi-layer construction with a bottom layer of silicone and top layer of hydrogel are also known. Biodegradable or semi-biodegradable arrays, however, are not likely suitable for instraspinal or intracortical microstimulation/recording techniques given that the base would need to biodegrade before the patient wakes up from surgery and begins moving, and the swelling progression that is integral to the biodegradation process may disturb the electrodes themselves.
There is a need, therefore, for a flexible-base electrode array that may be suitable for accurate mechanical and geometrical interfacing with a variety of neural tissue such as, for example, spinal cord tissue. Such an array may be biocompatible with the neural tissue, capable of conforming to the surface of the tissue and undergoing similar deformation to the tissue during normal daily movement. Such an array may be used for ISMS treatment.
To date, the interaction of known microelectrode arrays with spinal cord tissue as well as their stability in the cord, particularly for long-term use, remains unknown. As such, the ability to test and develop flexible-based electrode arrays that are mechanically biocompatible with various types of neural tissue, readily and accurately implantable as one single unit, without impeding the natural motion of the tissue or causing damage, is critical.
Historically, testing of neuroprosthetic array interfacing has been tested using actual samples of neural tissue. However, some known surrogate tissue models have been developed using different types of silicone elastomer in an attempt to mimic the mechanical properties of real neural tissue, such as spinal cord. One model comprises a SYLGARD® 527 silicone material that is capable of mimicking the ex vivo mechanical properties of human spinal cord in tension. Another model comprises QM Skin 30 silicone elastomer that is capable of simulating the mechanical properties of a human spinal cord in both tension and compression. Neither surrogate tissue, however, is capable of undergoing the extensive deformations that occur in a real spinal cord during identical loading conditions.
Other known surrogate tissue models comprise a collagen casing with an uncrosslinked gelatin filling. For example, attempts to optimize collagen models of spinal cord tissue were made by exposing both the surrogate cord material and in vivo feline cords to the impact of a falling mass and then matching the deformation behavior by adjusting relative concentrations of gelatin to water.
Gelatin filled-type spinal cord models, however, are designed to match the mechanical properties of a real cord in tension and/or compression such that the cord can be embedded with transducers to investigate the mechanisms underlying tissue injury. They are not suitable for use with interfacing microelectrode arrays or for evaluating the mechanical interactions between delicate ISMS microwires or implantable neurostimulators and the spinal cord. More specifically, currently known spinal cord models fail to address the importance of understanding the surface properties of the surrogate material, and the friction that occurs between the array and the cord. These properties can be important in determining how an electrode array may respond when the cord is deformed.
It is understood that relative and non-synergistic movement between an electrode array and its corresponding target tissue during long-term implantation of the array could induce stress and cause potential damage to the tissue. It is desirable to develop an electrode array having improved mechanical biocompatibility (e.g. minimal influence or impact on the tissue itself), and capable of long-term implantation directly into the target neural tissue. The use of such an array would reduce the inaccurate and inefficient implantation of individual electrodes into the tissue, a process which is known to be long, tedious, and impractical.
Thus, there is a need for a physical model of neural tissue that can be used to accurately and effectively evaluate the implantability of electrode arrays. Such a surrogate model may comprise materials having suitable mechanical and surface properties, including surface and interfacial properties that closely match real neural tissue. Such a surrogate model may be used to evaluate the mechanical interactions between neuronal interfacing devices (e.g. flexible-base electrode arrays) and neural tissue, such as the spinal cord.